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. 2023 May 17;14:2806. doi: 10.1038/s41467-023-38443-3

Fig. 1. PRMT1 methylates cGAS and inhibits the cGAS/STING DNA sensing signaling.

Fig. 1

a PRMT1 interacts with and methylates cGAS. ADMA: asymmetric dimethylarginine. Immunoblot analysis of the HA immunoprecipitant and WCL derived from HEK293T cells that ectopically express HA-cGAS and GFP-PRMTs constructs. b Endogenous PRMT1 binds with cGAS. Immunoblot analysis of the immunoprecipitant derived from HeLa cells using either PRMT1 antibody or control IgG. c PRMT1 methylates cGAS in vitro. Purified GST-cGAS protein was incubated with PRMT1 protein and SAM for 1.5 hours, followed by immunoblot analysis with indicated antibodies. d PRMT1 methylates cGAS in an enzyme activity-dependent manner. Immunoblot analysis of the HA immunoprecipitant and WCL derived from HEK293T cells that ectopically express HA-cGAS and GFP-PRMT1 or indicated mutant constructs. e Inhibition of PRMT1 blocks cGAS methylation. Immunoblot analysis of the HA immunoprecipitant and WCL derived from HEK293T cells with the treatment of MS023 (6 µM) or GSK3368715 (6 µM) for 24 hours. f Stable overexpression of PRMT1 represses cGAS/STING DNA sensing signaling. HeLa cells stably expressing either GFP or HA-PRMT1 were stimulated with either HT-DNA (1×: 1 μg/mL; 2×: 2 μg/mL), or ISD (0.2 μg/mL) for 12 hours, followed by immunoblot analysis. g Immunoblot analysis of HeLa stable cell lines that expresses either GFP, HA-PRMT1-WT, or the catalytic-dead mutant HA-PRMT1-E162Q, with or without stimulation with HT-DNA (1 μg/mL) for 12 hours, followed by immunoblot analysis. h PRMT1 overexpression reduces DNA-stimulated cGAMP production. HeLa stable cells lines as in f were stimulated with 1 μg/mL of HT-DNA for 12 hours, followed by ELISA analysis to measure cGAMP levels. n = 3. i PRMT1 overexpression reduces DNA-stimulated expression of type I/II interferon response genes. HeLa stable cell lines as in f were stimulated with 1 μg/mL of HT-DNA for 12 hours, followed by qPCR analysis to measure the mRNA levels of CCL5 and CXCL10. n = 4. Data are presented as mean values ± SD for h and i. Two-tailed unpaired Student t test were used in h and i. Source data are provided as a Source Data file.